Friday, February 20, 2015

Leiomyosarcoma Case Report

Clinical Presentation:
A 9 year old male castrated Labrador Retriever presented to the emergency service for vomiting, lethargy and discomfort.  The day prior to presentation, he started vomiting and had been evaluated by his primary veterinarian.  He was treated on an out-patient basis with supportive therapy (Maropitant, Metronidazole and a bland diet).
He continued to vomit overnight and was reevaluated by his primary veterinarian. He was depressed, had pale mucus membranes and bloodwork revealed hyperglycemia (129mg/dl, N:75-125), decreased sodium (139 mEq/l; N:141-152), mild anemia(Hct: 36.2%; :N:37-55), and thrombocytopenia (151 10^3/uL; N:200-500).  Abdominal radiographs revealed a soft tissue mass effect cranial ventral to the stomach on the lateral view and decreased contrast.  Thoracic radiographs had no significant findings.  
He was referred to HopeVS’s emergency service for further treatment. A cursory emergency ultrasound documented mild peritoneal effusion and a mixed echogenic mass in the cranial abdomen. An abdominocentesis revealed nonclotting hemorrhagic effusion with a PCV of 49% and Total Solids of 5.8 g/dl.   Extended data base noted increased lactate of 2.7 (0.6-2.5) and PCV: 37%/TS: 6.4g/dl.  Coagulation profiles (PT/PTT) were within normal limits.
A complete abdominal ultrasound revealed a very large mass along the lesser curvature of the stomach measuring 6-8 cm in thickness and 12-16 cm in length.  The mass was partially compartmentalized and occasionally cavitated but primarily consisted of a semi-solid disorganized clump of coalescing hyper and hypoechoic material that was closely associated with the gastric wall causing the lesser curvature to be concave and occasionally effacing the layers of the gastric wall. The was no direct evidence of a transmural lesion or of perforation.  Portions of the mass close to the gastric wall were variably vascular though the majority of the mass was avascular.  Several large pockets of faintly echogenic effusion throughout the ventral abdomen and the fat, omentum and mesentery were hyperechoic throughout the cranial abdomen surrounding the gastric mass. (Figure 1) After consultation with the owner, an abdominal exploratory with resection of the mass was recommended.
Surgery:
The patient was placed in dorsal recumbency and the ventral abdomen was clipped and prepped using standard aseptic technique.  A ventral abdominal incision was made and approximately 500 mls of hemorrhagic effusion  was removed from the abdomen.  (Figure 2) Exploration of the abdomen revealed bleeding from a small break in the serosal surface on the ventral aspect of the stomach.  Approximately 1/2 of the stomach palpated irregular (mildly thickened) and was bruised.  The bruising extended around the majority of the pylorus and into the beginning of the duodenum on the dorsal aspect of the stomach.  The remainder of the abdomen appeared normal.  A pylorectomy was performed obtaining 1 cm margins around the bruised, thickened area followed by a gastroduodenostomy (Billroth I).  Care was taken to assure that the biliary system was not disrupted.  The major duodenal papilla was identified and was ~ 1 cm from the site of resection of the proximal duodenum.  The gallbladder was easily expressed.  A liver biopsy was obtained from the left lateral liver lobe using a guillotine method and the abdomen was closed routinely.  All resected tissue, including the draining lymph node, was submitted for histopathology.   
Histopathology:
No significant lesions were noted in the liver or lymph node biopsies. Within the gastrointestinal tract an acute mural hematoma was noted with, mild lymphoplasmacytic gastritis and the presence of helicobacter. Further gross evaluation revealed a small white, firm nodule (1cm in diameter) at the periphery of the hematoma but within the gastric wall.  Within this section, the wall was expanded by an unencapsulated neoplastic moderately to highly cellular proliferation of spindle cells arranged in interwoven bundles.  The cells were described as elongated to cigar shaped nuclei with stippled chromatin and small to moderate amounts of eosinophilic cytoplasm with indistinct cell borders.  Anisokaryosis was mild to moderate and mitotic activity was 44  per 10 high power fields.  There was multifocal necrosis within the lesion containing accumulations of eosinophilic and karyorrhectic debris.  There are dense infiltrates of small well differentiated lymphocytes and fibroplasia along the periphery of the tumor.  The mass was greater than 5mms from a surgical margin. A diagnosis of a high grade sarcoma was made with the differentials of a leiomyosarcoma and gastrointestinal stromal tumor.  Immunohistochemistry staining was negative for C-Kit, confirming a diagnosis of a high grade leiomyosarcoma. 
Treatment:
The patient recovered uneventfully post-surgery and was discharged at 4 days post- surgery.  A follow oncology consultation was performed and systemic therapy with Doxorubicin IV q 3 weeks for 4-5 cycles was recommended since the tumor was deemed high grade. A baseline abdominal ultrasound was performed prior to starting chemotherapy at 28 days postop and no overt evidence of recurrence was noted. The patient has received 2 cycles thus far with little issues noted.
Overview:
Gastric tumors make up approximately 1-3% of malignant neoplasia in dogs and cats. In dogs, the most common gastric tumor is gastric adenocarcinoma, which accounts for 42-72% of malignant gastric neoplasia.  Leiomyosarcoma, a tumor of smooth muscle,  is the second most common type of gastrointestinal tumor in dogs but it occurs much less frequently than adenocarcinoma.  It can occur anywhere in the gastrointestinal tract but occurs most commonly in the stomach and small intestine. Clinical signs are influenced by tumor location and can include vomiting, weight loss, inappetence, melena, lethargy, hematochezia and hematemesis. Perforation of the intestinal wall secondary to tumor infiltration has been reported but is more common with gastrointestinal stromal tumors than leiomyosarcomas.  A hemoabdomen, as noted in this patient’s history, is not a common finding.
Imaging modalities most commonly used to evaluate a gastric mass include radiography (+/-contrast), ultrasonography and endoscopy.  In addition, when working up a gastric mass, three view thoracic radiographs, abdominal ultrasound and full blood work are recommended to look for any evidence of spread, and evaluate for any concurrent disease.  Paraneoplastic  hypoglycemia has been reported in dogs with leiomyosarcoma.  The exact mechanism is unclear ,but it is normally reversible following surgical treatment.
Surgical excision is the initial treatment of choice for gastric leimyosarcoma.  Also, at the time of surgical exploration, biopsy of the draining lymph node is recommended.  Histopathology with margin evaluate should be performed in all cases as adjuvant treatment recommendations will be made based on the margins and aggressiveness of the lesion.   
On histopathologic evaluation, gastrointestinal stromal tumors and leiomyosarcoma have a similar appearance.  Gastrointestinal stromal tumors arise from the interstitial cells of Cajal.  They express the CD117 (c-KIT) transmembrane receptor and therefore stain positive on c-KIT immunohistochemistry staining.  Leiomyosarcoma is negative for CD117.  Therefore, c-KIT immunohistochemistry staining is often used to differentiate between the two types of neoplasia. 
Currently there is not a published prognostically relevant grading scheme for gastric leiomyosarcoma specifically, but in cutaneous and subcutaneous soft tissue sarcomas,  grade is based on differentiation, necrosis and mitotic activity.    If considered low or moderate grade with clean margins, there is low chance for spread in general with sarcomas and surgery alone is recommended with no further adjuvant treatment postop.  If sarcomas, including leiomyosarcoma, are considered high grade, even with complete excision, chemotherapy is recommended, however data regarding efficacy is lacking.
In one study, 10 dogs with gastrointestinal leiomyosarcoma, a median survival time of 7.8 months was noted with surgery alone was noted, however, only 3 of the 10 dogs had gastric leiomyosarcoma.  Currently, no large scale studies exist comparing survival times in dogs treated with surgery alone vs. surgery and adjuvant chemotherapy.

Submitted by Dr. Lauren May VMD, DACVS

References:
Bacon N. Soft Tissue Sarcomas. In: Dobson JM, Lascelles BDX, eds. BSAVA Manual of Canine and Feline Oncology. 3rded. Gloucester: BSAVA, 2011;178-190.
Culp WTN, Cavanaugh RP, et al. Alimentary tract. In: Kudnig ST, Sequin B, eds. Veterinary Surgical Oncology. UK: Wiley-Blackwell, 2012;179-271.
Dennis MM, McSporran KD, et al. Prognostic factors for cutaneous and subcutaneous soft tissue sarcomas in dogs. Vet Pathol 2011;48(1):73-84.
Kuntz CA, Dernell WS, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc 1997;211:1147–1151.
Liptak JM, Forrest LJ. Soft Tissue Sarcomas. In: Withrow ST, Vail DM, eds. Withrow & MacEwen’s Small Animal Clinical Oncology. 4th ed. St. Louis: Saunders Elsevier, 2007; 425-449.
Russell KN, Mehler SJ, et al. Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs 42 cases (1990-2003) J Am Vet Med Assoc 2007;230:1329-33.

Figures:
Figure 1. Ultrasound image showing in cross section the proximity of the mass to the pylorus. The mass is indicated by the red arrow and the pylorus is labeled by the white arrow.
Figure 2
Intraoperative photo showing stomach wall with severe bruising.  Region of stomach wall that had been bleeding is indicated by black arrow. 



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